Chiroptical spectroscopic methods will be utilized to probe molecular structure and intermolecular interactions in solution. The general procedure will involve the comparison of experimental circular dichroism spectra with the results of theoretical calculations carried out by means of a theory that utilizes spectroscopic data determined from studies of small molecules to calculate the optical properties of macromolecules. The applicability of the method to a given chromophoric group is first tested with relatively small model compounds. It is then applied to the same chromophoric groups in macromolecules, especially proteins, Specifically, the side chain chromophores of proteins which absorb in the near-UV region will be utilized to probe local structure and environment. The technique will be used to compare the structure assumed by the protein in solution with that determined by means of X-ray diffraction studies of crystals, and to investigate the binding of inhibitors and substrates to enzymes. The proteins which will be investigated will include ribonuclease, several lysozymes, staphylococcal nuclease, and pancreatic trypsin inhibitor.